Systemic inflammation as a novel QT-prolonging risk factor in patients with torsades de pointes

Lazzerini, Pietro Enea; Laghi‐Pasini, Franco; Bertolozzi, Iacopo; Morozzi, Gabriella; Lorenzini, Sauro; Simpatico, Antonella; Selvi, Enrico; Bacarelli, Maria Romana; Finizola, Francesco; Vanni, Francesca; Lazaro, Deana; Aromolaran, Ademuyiwa S.; Sherif, Nabil El; Boutjdir, Mohamed; Capecchi, Pier Leopoldo

doi:10.1136/heartjnl-2016-311079

Cited by 100 publications

(91 citation statements)

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“…concentrations. 4 We also demonstrated that in 40 unselected TdP patients, elevated IL-6 levels were present, comparable to those observed in severe active rheumatoid arthritis (RA), and 15-20 times higher than controls. 4 In the light of the above considerations, dampening the systemic inflammatory response in COVID-19 might be crucial not only to control lung involvement, but also to reduce acute cardiovascular complications, including QT-related arrhythmic events, both possibly affecting short-term mortality.…”

Section: Coronavirus Disease 2019 (Covid-19) Is Caused By the Severe supporting

confidence: 58%

“…4 We also demonstrated that in 40 unselected TdP patients, elevated IL-6 levels were present, comparable to those observed in severe active rheumatoid arthritis (RA), and 15-20 times higher than controls. 4 In the light of the above considerations, dampening the systemic inflammatory response in COVID-19 might be crucial not only to control lung involvement, but also to reduce acute cardiovascular complications, including QT-related arrhythmic events, both possibly affecting short-term mortality. In particular, it may be pivotal to block the IL-6 pathway as data suggest a potential beneficial effect of the anti-IL-6 receptor monoclonal-antibody tocilizumab on COVID-inflammatory cytokines associated with QTc prolongation, 2 tocilizumab led to a rapid and significant QTc shortening, which correlated with both the decrease in CRP and cytokine levels.…”

Section: Coronavirus Disease 2019 (Covid-19) Is Caused By the Severe supporting

confidence: 58%

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COVID-19, Arrhythmic Risk, and Inflammation

2020

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Section: Coronavirus Disease 2019 (Covid-19) Is Caused By the Severe supporting

confidence: 58%

Section: Coronavirus Disease 2019 (Covid-19) Is Caused By the Severe supporting

confidence: 58%

COVID-19, Arrhythmic Risk, and Inflammation

2020

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“…Moreover, in people with rheumatoid arthritis, IL‐6 inhibitor therapy results in rapid QTc shortening in 3–6 months (Capecchi et al, ; Kobayashi et al, ; Lazzerini et al, ). Also recently described were 40 unselected patients with unexplained torsade de pointes in whom IL‐6 concentrations were markedly elevated at levels equivalent to those with severe rheumatoid arthritis (Lazzerini et al, ). In an in vitro study of guinea pig ventricular cardiomyocytes using electrophysiological and biochemical assays, IL‐6 suppressed the delayed rectifier potassium current and prolonged the action potential duration (Aromolaran et al, ).…”

Section: Discussionmentioning

confidence: 99%

Associations between QT interval subcomponents, HIV serostatus, and inflammation

Bhondoekhan

Haberlen

et al. 2019

Noninvasive Electrocardiol

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Background The total QT interval comprises both ventricular depolarization and repolarization currents. Understanding how HIV serostatus and other risk factors influence specific QT interval subcomponents could improve our mechanistic understanding of arrhythmias. Methods Twelve‐lead electrocardiograms (ECGs) were acquired in 774 HIV‐infected (HIV+) and 652 HIV‐uninfected (HIV−) men from the Multicenter AIDS Cohort Study. Individual QT subcomponent intervals were analyzed: R‐onset to R‐peak, R‐peak to R‐end, JT segment, T‐onset to T‐peak, and T‐peak to T‐end. Using multivariable linear regressions, we investigated associations between HIV serostatus and covariates, including serum concentrations of inflammatory biomarkers such as interleukin‐6 (IL‐6), and each QT subcomponent. Results After adjustment for demographics and risk factors, HIV+ versus HIV− men differed only in repolarization phase durations with longer T‐onset to T‐peak by 2.3 ms (95% CI 0–4.5, p < .05) and T‐peak to T‐end by 1.6 ms (95% CI 0.3–2.9, p < .05). Adjusting for inflammation attenuated the strength and significance of the relationship between HIV serostatus and repolarization. The highest tertile of IL‐6 was associated with a 7.3 ms (95% CI 3.2–11.5, p < .01) longer T‐onset to T‐peak. Age, race, body mass index, alcohol use, and left ventricular hypertrophy were each associated with up to 2.2–12.5 ms longer T‐wave subcomponents. Conclusions HIV seropositivity, in combination with additional risk factors including increased systemic inflammation, is associated with longer T‐wave subcomponents. These findings could suggest mechanisms by which the ventricular repolarization phase is lengthened and thereby contribute to increased arrhythmic risk in men living with HIV.

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“…Data from patients with chronic autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, and inflammatory bowel diseases27 28 and from the general population29 support an association between systemic inflammation levels and lengthening of the QTc interval. Inflammatory cytokines may directly affect the myocardium by inducing changes in potassium and calcium ion channel expression and function 28. Alternatively, heightened systemic inflammation may lead to autonomic nervous system dysfunction that can then result in QT prolongation 27…”

Section: Discussionmentioning

confidence: 99%

Predictors of electrocardiographic QT interval prolongation in men with HIV

Zhang

Haberlen

et al. 2018

Heart

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ObjectiveHIV-infected (HIV+) individuals may be at increased risk for sudden arrhythmic cardiac death. Some studies have reported an association between HIV infection and prolongation of the electrocardiographic QT interval, a measure of ventricular repolarisation, which could potentiate ventricular arrhythmias. We aimed to assess whether HIV+ men have longer QT intervals than HIV-uninfected (HIV−) men and to determine factors associated with QT duration.MethodsWe performed resting 12-lead ECGs in 774 HIV+ and 652 HIV− men in the Multicenter AIDS Cohort Study (MACS). We used multivariable linear and logistic regression analyses to assess associations between HIV serostatus and Framingham corrected QT interval (QTc), after accounting for potential confounders. We also determined associations among QTc interval and HIV-related factors in HIV+ men. In a subgroup of participants, levels of serum markers of inflammation were also assessed.ResultsAfter adjusting for demographics and risk factors, QTc was 4.0 ms longer in HIV+ than HIV− men (p<0.001). Use of antiretroviral therapy (ART), specific ART drug class use and other HIV-specific risk factors were not associated with longer QTc. Among the subgroup with inflammatory biomarker measurements, higher interleukin-6 (IL-6), intercellular adhesion molecule-1 (ICAM-1) and B-cell activating factor levels were independently associated with longer QTc and their inclusion partially attenuated the HIV effect.ConclusionsHIV+ men had longer QTc, which was associated with higher levels of systemic inflammatory factors. This longer QTc may contribute to the increased risk for sudden arrhythmic cardiac death in some HIV+ individuals.

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Systemic inflammation as a novel QT-prolonging risk factor in patients with torsades de pointes

Abstract: The data are first to show that systemic inflammation via elevated IL-6 levels may represent a novel QT-prolonging risk factor contributing to TdP occurrence in the presence of other classical risk factors. If confirmed, this could open new avenues in antiarrhythmic therapy.

Cited by 100 publications

References 28 publications

COVID-19, Arrhythmic Risk, and Inflammation

COVID-19, Arrhythmic Risk, and Inflammation

Associations between QT interval subcomponents, HIV serostatus, and inflammation

Predictors of electrocardiographic QT interval prolongation in men with HIV

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